Skip to main content
SpringerLink
Log in

Brain Glycogen Decreases During Intense Exercise Without Hypoglycemia: The Possible Involvement of Serotonin

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Brain glycogen stored in astrocytes, a source of lactate as a neuronal energy source, decreases during prolonged exercise with hypoglycemia. However, brain glycogen dynamics during exercise without hypoglycemia remain unknown. Since intense exercise increases brain noradrenaline and serotonin as known inducers for brain glycogenolysis, we hypothesized that brain glycogen decreases with intense exercise not accompanied by hypoglycemia. To test this hypothesis, we employed a well-established acute intense exercise model of swimming in rats. Rats swam for fourteen 20 s bouts with a weight equal to 8 % of their body mass and were sacrificed using high-power (10 kW) microwave irradiation to inactivate brain enzymes for accurate detection of brain glycogen and monoamines. Intense exercise did not alter blood glucose, but did increase blood lactate levels. Immediately after exercise, brain glycogen decreased and brain lactate increased in the hippocampus, cerebellum, cortex, and brainstem. Simultaneously, serotonin turnover in the hippocampus and brainstem mutually increased and were associated with decreased brain glycogen. Intense swimming exercise that does not induce hypoglycemia decreases brain glycogen associated with increased brain lactate, implying an importance of glycogen in brain energetics during intense exercise even without hypoglycemia. Activated serotonergic regulation is a possible underlying mechanism for intense exercise-induced glycogenolysis at least in the hippocampus and brainstem.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Belanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14:724–738

    Article  CAS  PubMed  Google Scholar 

  2. Matsui T, Ishikawa T, Ito H, Okamoto M, Inoue K, Lee MC, Fujikawa T, Ichitani Y, Kawanaka K, Soya H (2012) Brain glycogen supercompensation following exhaustive exercise. J Physiol 590:607–616

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Matsui T, Soya S, Okamoto M, Ichitani Y, Kawanaka K, Soya H (2011) Brain glycogen decreases during prolonged exercise. J Physiol 589:3383–3393

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Kong J, Shepel PN, Holden CP, Mackiewicz M, Pack AI, Geiger JD (2002) Brain glycogen decreases with increased periods of wakefulness: implications for homeostatic drive to sleep. J Neurosci 22:5581–5587

    CAS  PubMed  Google Scholar 

  5. Cruz NF, Dienel GA (2002) High glycogen levels in brains of rats with minimal environmental stimuli: implications for metabolic contributions of working astrocytes. J Cereb Blood Flow Metab 22:1476–1489

    Article  CAS  PubMed  Google Scholar 

  6. Brown AM (2004) Brain glycogen re-awakened. J Neurochem 89:537–552

    Article  CAS  PubMed  Google Scholar 

  7. Sickmann HM, Schousboe A, Fosgerau K, Waagepetersen HS (2005) Compartmentation of lactate originating from glycogen and glucose in cultured astrocytes. Neurochem Res 30:1295–1304

    Article  CAS  PubMed  Google Scholar 

  8. Secher NH, Seifert T, Van Lieshout JJ (2008) Cerebral blood flow and metabolism during exercise: implications for fatigue. J Appl Physiol 104:306–314

    Article  CAS  PubMed  Google Scholar 

  9. Ide K, Schmalbruch IK, Quistorff B, Horn A, Secher NH (2000) Lactate, glucose and O2 uptake in human brain during recovery from maximal exercise. J Physiol 522:159–164

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Larsen TS, Rasmussen P, Overgaard M, Secher NH, Nielsen HB (2008) Non-selective beta-adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans. J Physiol 586:2807–2815

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Miura H, Naoi M, Nakahara D, Ohta T, Nagatsu T (1996) Effects of moclobemide on forced-swimming stress and brain monoamine levels in mice. Pharmacol Biochem Behav 53:469–475

    Article  CAS  PubMed  Google Scholar 

  12. Renard CE, Dailly E, David DJ, Hascoet M, Bourin M (2003) Monoamine metabolism changes following the mouse forced swimming test but not the tail suspension test. Fundam Clin Pharmacol 17:449–455

    Article  CAS  PubMed  Google Scholar 

  13. Hutchins DA, Rogers KJ (1970) Physiological and drug-induced changes in the glycogen content of mouse brain. Br J Pharmacol 39:9–25

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS (2008) Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration. Endocrinology 149:1499–1504

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Canada SE, Weaver SA, Sharpe SN, Pederson BA (2011) Brain glycogen supercompensation in the mouse after recovery from insulin-induced hypoglycemia. J Neurosci Res 89:585–591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Rasmussen P, Vedel JC, Olesen J, Adser H, Pedersen MV, Hart E, Secher NH, Pilegaard H (2011) In humans IL-6 is released from the brain during and after exercise and paralleled by enhanced IL-6 mRNA expression in the hippocampus of mice. Acta Physiol 201:475–482

    Article  CAS  Google Scholar 

  17. Kawanaka K, Tabata I, Tanaka A, Higuchi M (1998) Effects of high-intensity intermittent swimming on glucose transport in rat epitrochlearis muscle. J Appl Physiol 84:1852–1857

    CAS  PubMed  Google Scholar 

  18. Koshinaka K, Kawasaki E, Hokari F, Kawanaka K (2009) Effect of acute high-intensity intermittent swimming on post-exercise insulin responsiveness in epitrochlearis muscle of fed rats. Metabolism 58:246–253

    Article  CAS  PubMed  Google Scholar 

  19. Scheurink AJ, Steffens AB, Dreteler GH, Benthem L, Bruntink R (1989) Experience affects exercise-induced changes in catecholamines, glucose, and FFA. Am J Physiol 256:R169–R173

    CAS  PubMed  Google Scholar 

  20. Watanabe T, Morimoto A, Sakata Y, Long NC, Murakami N (1991) Prostaglandin E2 is involved in adrenocorticotrophic hormone release during swimming exercise in rats. J Physiol 433:719–725

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Wada M, Morimoto A, Watanabe T, Sakata Y, Murakami N (1990) Effects of physical training on febrile and acute-phase responses induced in rats by bacterial endotoxin or interleukin-1. J Physiol 430:595–603

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Terada S, Yokozeki T, Kawanaka K, Ogawa K, Higuchi M, Ezaki O, Tabata I (2001) Effects of high-intensity swimming training on GLUT-4 and glucose transport activity in rat skeletal muscle. J Appl Physiol 90:2019–2024

    CAS  PubMed  Google Scholar 

  23. Hirano M, Rakwal R, Shibato J, Agrawal GK, Jwa NS, Iwahashi H, Masuo Y (2006) New protein extraction/solubilization protocol for gel-based proteomics of rat (female) whole brain and brain regions. Mol Cells 22:119–125

    CAS  PubMed  Google Scholar 

  24. Passonneau JV, Lauderdale VR (1974) A comparison of three methods of glycogen measurement in tissues. Anal Biochem 60:405–412

    Article  CAS  PubMed  Google Scholar 

  25. Wang L, Dong Y, Yu X, Shangguan DH, Zhao R, Han HW, Liu GQ (2002) Analysis of glucose and lactate in dialysate from hypothalamus of rats after exhausting swimming using microdialysis. Biomed Chromatogr 16:427–431

    Article  CAS  PubMed  Google Scholar 

  26. Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810–823

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Newman LA, Korol DL, Gold PE (2011) Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS ONE 6:e28427

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Brooks GA (1986) The lactate shuttle during exercise and recovery. Med Sci Sports Exerc 18:360–368

    Article  CAS  PubMed  Google Scholar 

  29. Hertz L, Gibbs ME, Dienel GA (2014) Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline. Front Neurosci 8:261

    Article  PubMed Central  PubMed  Google Scholar 

  30. Shulman RG, Hyder F, Rothman DL (2001) Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proc Natl Acad Sci USA 98:6417–6422

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Walls AB, Heimburger CM, Bouman SD, Schousboe A, Waagepetersen HS (2009) Robust glycogen shunt activity in astrocytes: effects of glutamatergic and adrenergic agents. Neuroscience 158:284–292

    Article  CAS  PubMed  Google Scholar 

  32. Obel LF, Muller MS, Walls AB, Sickmann HM, Bak LK, Waagepetersen HS, Schousboe A (2012) Brain glycogen-new perspectives on its metabolic function and regulation at the subcellular level. Front Neuroenerg 4:3

    Article  CAS  Google Scholar 

  33. Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219–249

    Article  CAS  PubMed  Google Scholar 

  34. Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim FJ, Goldman SA, Nedergaard M (2007) The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 27:12255–12266

    Article  CAS  PubMed  Google Scholar 

  35. Mangia S, Giove F, Dinuzzo M (2013) K+ homeostasis in the brain: a new role for glycogenolysis. Neurochem Res 38:470–471

    Article  CAS  PubMed  Google Scholar 

  36. Hertz L, Xu J, Song D, Du T, Li B, Yan E, Peng L (2015) Astrocytic glycogenolysis: mechanisms and functions. Metab Brain Dis 30:317–333

    Article  CAS  PubMed  Google Scholar 

  37. Muller MS (2014) Functional impact of glycogen degradation on astrocytic signalling. Biochem Soc Trans 42:1311–1315

    Article  PubMed Central  PubMed  Google Scholar 

  38. Magistretti PJ (1988) Regulation of glycogenolysis by neurotransmitters in the central nervous system. Diabete Metab 14:237–246

    CAS  PubMed  Google Scholar 

  39. Moruzzi G, Magoun HW (1949) Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1:455–473

    Article  CAS  PubMed  Google Scholar 

  40. Ohiwa N, Saito T, Chang H, Omori T, Fujikawa T, Asada T, Soya H (2006) Activation of A1 and A2 noradrenergic neurons in response to running in the rat. Neurosci Lett 395:46–50

    Article  CAS  PubMed  Google Scholar 

  41. Colgan LA, Cavolo SL, Commons KG, Levitan ES (2012) Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites. J Neurosci 32:15737–15746

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Huang HP, Zhu FP, Chen XW, Xu ZQ, Zhang CX, Zhou Z (2012) Physiology of quantal norepinephrine release from somatodendritic sites of neurons in locus coeruleus. Front Mol Neurosci 5:29

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Marcussen AB, Flagstad P, Kristjansen PE, Johansen FF, Englund U (2008) Increase in neurogenesis and behavioural benefit after chronic fluoxetine treatment in Wistar rats. Acta Neurol Scand 117:94–100

    CAS  PubMed  Google Scholar 

  44. Mayberg HS, Silva JA, Brannan SK, Tekell JL, Mahurin RK, McGinnis S, Jerabek PA (2002) The functional neuroanatomy of the placebo effect. Am J Psychiatry 159:728–737

    Article  PubMed  Google Scholar 

  45. Gibbs ME, Hertz L (2014) Serotonin mediation of early memory formation via 5-HT2B receptor-induced glycogenolysis in the day-old chick. Front Pharmacol 5:54

    Article  PubMed Central  PubMed  Google Scholar 

  46. Duran J, Saez I, Gruart A, Guinovart JJ, Delgado-Garcia JM (2013) Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. J Cereb Blood Flow Metab 33:550–556

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Lee MC, Inoue K, Okamoto M, Liu YF, Matsui T, Yook JS, Soya H (2013) Voluntary resistance running induces increased hippocampal neurogenesis in rats comparable to load-free running. Neurosci Lett 537:6–10

    Article  CAS  PubMed  Google Scholar 

  48. Lee MC, Okamoto M, Liu YF, Inoue K, Matsui T, Nogami H, Soya H (2012) Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNF signaling. J Appl Physiol 113:1260–1266

    Article  PubMed  Google Scholar 

  49. Contarteze RV, Manchado Fde B, Gobatto CA, De Mello MA (2008) Stress biomarkers in rats submitted to swimming and treadmill running exercises. Comp Biochem Physiol A Mol Integr Physiol 151:415–422

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge Yukio Ichitani (University of Tsukuba) for his technical assistance for the microwave irradiation. This study was supported, in part, by a Grant-in-Aid for Challenging Exploratory Research of the Japan Society for the Promotion of Science (JSPS); a Grant-in-Aid for JSPS Fellows and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) for the Body and Mind Integrated Sports Sciences (BAMIS) Project (2010–2013); and the Human High Performance (HHP) project (2014). T.M. was supported as a JSPS Research Fellow-SPD (2012–2014).

Conflict of interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Laboratory of Exercise Biochemistry and Neuroendocrinology, Institute for Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8574, Japan

    Takashi Matsui, Shingo Soya & Hideaki Soya

  2. Department of Health and Nutrition, Niigata University of Health and Welfare, Niigata City, Niigata, 950-3198, Japan

    Takashi Matsui & Kentaro Kawanaka

Authors
  1. Takashi Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shingo Soya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kentaro Kawanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hideaki Soya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideaki Soya.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 134 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsui, T., Soya, S., Kawanaka, K. et al. Brain Glycogen Decreases During Intense Exercise Without Hypoglycemia: The Possible Involvement of Serotonin. Neurochem Res 40, 1333–1340 (2015). https://doi.org/10.1007/s11064-015-1594-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1594-1

Keywords

Search

Navigation